The objective of this program project is to provide an understanding of the mechanisms of adaptation between a transplanted heart and the recipient, and to improve the long- term management of these individuals. The rationale for this work is that the current short-term management of such patients is reasonably satisfactory (one-year survival rates of approximately 80-90%), but there remain long- term problems such as accelerated atherosclerosis, myocardial fibrosis, hypertension and impaired renal function. Such problems are disorders of immunosuppression and adaptation, and an improved understanding of the physiologic and immunologic mechanisms of adaptation and maladaptation will provide the basis for improved patient care. The specific aims are to study the processes of adaptation in cardiac transplantation in the following areas: 1. Physiologic Alterations A. Adrenergic Responsiveness and Receptor Function (Project 1) B. Cellular Electrophysiology and Pharmacology (Project 2) 2. Immunologic Alterations A. Studies in Adaptation in Experimental Cardiac Allografts and Xenografts (Project 3) B. Idiotypic Regulation of Allograft Immunity in Patients with Heart Transplants (Project 4) C. The Role of Cyclosporine Receptors in Cardiac Transplantation Project 5)